Hepatic stellate cell expression of alpha-smooth muscle actin: Role in recurrent hepatitis C virus in living donor liver transplantation

Abstract

Background: The alpha isotope of actin expressed by Hepatic stellate cells (HSCs) reflects their activation to myofibroblast-like cell and is directly related to liver fibrogenesis in chronic liver disease. Aim: To study the correlation between the activation of HSCs and the degree of fibrosis in patients with recurrent HCV chronic hepatitis after Living Donor Liver Transplantation (LDLT). Methods: A total of 69 biopsies from 17 patients with post transplant recurrent HCV hepatitis, 17 cirrhotic liver and 17 normal control liver were retrospectively studied. Paraffin sections of all 69 biopsies were stained with anti-alpha-smooth muscle actin antibody by immunoperoxidase method and semi-quantitatively evaluated. Liver fibrosis was assessed by Masson's trichrome stain. HCV-PTR patients received standard antiviral therapy. Results: The grade of alpha-smooth muscle actin-positive HSCs were significantly higher in the HCV-C group (35.3% G3, 35.3% G4) and HCV-PTR group (58.8% G1) compared to DL group (70.6% G0). HSCs activation preceded the detection of fibrous tissue deposition in some patients with HCV-PTR. There was a statistically significant correlation between the grade of HSCs and the stage of fibrosis in HCV-PTR group. After antiviral therapy HSC grade significantly decreased, in both clinically responders and non-responders; the decrease in HSC grade also correlated with the improvement in activity grade. HSCs increased after episodes of acute cellular rejection. Conclusion: Our study confirmed the value of alphasmooth muscle actin expression as a reliable marker of HSCs activation that could be useful to identify early stages of hepatic fibrosis and monitor the efficacy of therapy. In the presence of advanced cirrhosis other factors, rather than alpha-smooth muscle actin-positive HSC, may sustain fibrosis deposition.